S114: OUTCOME OF OLDER PATIENTS (&gt;55 YRS) WITH NEWLY DIAGNOSED PH/BCR:ABL POSITIVE ALL PROSPECTIVELY TREATED ACCORDING TO PEDIATRIC-BASED, AGE-ADAPTED GMALL PROTOCOLS
Authors: Fabian Lang, Heike Pfeifer, Simon Raffel, Walter Fiedler, Maher Hanoun, Mathias Hänel, Bernd Spriewald, Andreas Viardot, Vladan Vucinic, Hubert Serve, Dieter Hoelzer, Nicola Gökbuget
Journal: HemaSphere (2023)

Background: Outcome in younger patients (pts) with Philadelphia-positive Acute Lymphoblastic Leukemia (Ph+ ALL) has been improved by TKI with pediatric-based therapy and stem cell transplantation (SCT). In older pts the selection of tyrosine kinase inhibitor (TKI), the need for chemotherapy and antibody therapies is debated and new data from phase II trials are available. Aims: The German Multicenter Center Study Group for Adult ALL (GMALL) aimed to establish and evaluate standard of care therapies for older pts with Ph+ ALL (>55yrs). Methods: The GMALL has conducted a trial (NCT00198978) which was followed by a registry trial based on standard recommendations with prospective documentation in the GMALL registry (NCT02872987). Strategies were modified over the years. The backbone included: Pre-phase (Dexa, Cyclo), induction (Ind) I (Dexa, VCR, Idarubicine), induction II (Cyclo, ARAC), consolidation (C) cycles with HDMTX (± E.coli ASP), HDAraC (earlier: VM26), reinduction (VCR, Idarubicine, Cyclo, AraC), ± Rituximab in CD20+, i.th. prophylaxis and maintenance (6-MP/MTX). Induction was replaced by Imatinib (Ima) only (group 1), Ima was added to the standard induction (group 2) or combined with VCR/Dexa only (group 3). In addition, in group 3 MRD-based modification of TKI was recommended in all pts with MRD>10-4 after C II. Results: 305 pts from 105 sites were included between 2007 and 2022 (table 1). The median age was 66 (56-83) yrs. 46% were aged 56-65 yrs, 48% were 66-75 yrs and 7% > 75 yrs. 40% had at least one comorbidity according to the Charlson-Score (ChS); 6% had ≥3. 45% were male and 55% female. The CR rate after Ind was 87% with 6% early death (ED) and 7% failure or partial remission. CR rates were 88%, 87% and 81% in pts aged 56-65, 66-75, ≥76 yrs with ED rates 4%, 5% and 19% resp. (p=.08). Group 2 comprised only 15 pts and was not considered for comparison. CR rates did not correlate to ChS. MRD response data were available at week 10 in 89 pts, at week 17 in 102 pts and at week 24 in 68 pts. In CR patients the molecular CR (MolCR)/ failure (MolFail) rates were 11%/63%, 13%/52% and 32%/37% resp. The remaining pts had either low positive or non-quantifiable MRD. MRD response showed no correlation with remission duration (RD). With a median follow up of 1.6 yrs overall survival (OS) in the total cohort at 1, 3 and 5 yrs was 72%, 45% and 34% resp with a median OS of 2.6 years. In 259 CR pts RD was 76%, 40% and 27% after 1, 3 and 5 yrs. The mortality in CR was 6% and 21% of pts stopped backbone treatment in CR1. OS strongly correlated to age and was very poor in pts >75 yrs (23% OS at 3 yrs; table 1). ChS showed no influence on OS. OS tended to be superior in the last cohort (group 3 vs group 1), 55% vs 38% at 3 yrs (p=.18; Fig 1). The median OS was not reached in group 3. The same applied for RD (group 3 vs group 1: 61% vs 32%;.02). OS at 3 yrs correlated with age (54% vs 67% vs 23%; p=.12) also in group 3 (Fig 2). Overall, only 29% (N=77) of all CR pts received an allogeneic SCT in CR1. SCT pts showed a 3/5 yrs OS of 67%/55%. OS after SCT vs No SCT was significantly superior for SCT (68% vs 44%;p=.003). Summary/Conclusion: With this age-adapted regimen comprising low-chemotherapy Ind with Ima followed by pediatric-based C, a reasonable CR rate was achieved up to the age of 75 yrs. ChS had no impact on OS and mortality in CR was limited, underlining the good tolerability of this regimen. However, the rates of MRD response were limited and SCT in selected pts had superior results. The improved outcome in the last cohort, which implied MRD based treatment modifications indicates the opportunities of further improvement of this standard backbone.Keywords: Tyrosine kinase inhibitor, Acute lymphoblastic leukemia, Elderly, BCR::ABL